The long-term goal of the proposed research is to use biochemical and cell biological approaches including morphological and cell fractionation techniques to analyze structurally and functionally the integrative mechanism by which insulin regulates adipocyte metabolism. Particular emphasis will be placed on understanding the mechanism of insulin action. The key areas to be studied will be: 1) insulin-receptor interactions using 125I-insulin and monomeric ferritin-insulin to study hormone binding, degradation, uptake and their relationships of all this to biological activity. In addition studies will be performed to determine the fate of the insulin receptor during the uptake process. The use of anti-receptor antibodies as well as anti-intramembranous particle antibodies will be of help in these studies. 2) to characterize the hormonal alterations of calcium content in various subcellular compartments by electron histochemical techniques and x-ray microprobe analysis.